Cartilage is a very specialized tissue containing only one cell type, the chondrocyte. Chondrocyte metabolism and function are influenced by the composition of the extracellular environment (Oxygen tension, pH, ionic concentration), the extracellular matrix composition, the matrix-cell interactions and the physical signals (stress and stain) transmitted across the articular surfaces of the joint. The failure of cartilage to regenerate itself is believed to be one of the fundamental pathways in the pathophysiology of degenerative osteoarthritis. The goals of this study are: - to determine the utility of non-invasive imaging techniques for early detection and longitudinal progression of age-related degenerative joint disease in a non-human primate model for spontaneous osteoarthritis; and - to examine the reparative potential of chondrocytes taken from aging non-human primates at various stages of joint degeneration. Progress during the past year: To date, approximately twenty pairs of non-human primate knees and hands have been collected from the NIH tissue bank. Several of the specimens have been imaged by micro-CT and micro-MRI. These results indicate that 4.7T micro-MRI and micro-CT can be used in the early detection of microscopic changes in the bone and cartilage in early degenerative disease of cartilage and bone respectively. These methods are also valuable in the long-term studies of disease progression, to quantify joint destruction, osteophyte formation and changes in bone mineral density in the non-human primate model for spontaneous OA. During the past year, our quantitative and qualitative assessment of articular cartilage using the atomic force microscope (AFM) have confirmed the feasibility of the proposed studies of the cartilage surface, the chondrocyte cytoskeleton, and the subchondral bone. We plan to continue these studies in an attempt to demonstrate alterations or deformations in the cartilage ECM. The AFM will be used to: - study the surface topography, collagen structural lattice and the mechanical properties of intact articular cartilage; - assess the functional properties of both intact cartilage tissues, and the isolated chondrocytes; - examine the physical properties (lubrication, sheer stress, surface charge, elasticity, collagen fiber size and orientation) of aging articular cartilage; and - assess and/or quantitate these characteristics as a function of tissue and cellular aging as it relates to OA.